Absorption, Distribution and Excretion
The systemic absorption and mechanism of action of estradiol are not fully understood. Estrogen diffuses into target cells and interacts with protein receptors. Target cells include the female reproductive tract, mammary glands, hypothalamus, and pituitary gland. Estrogen increases the synthesis of sex hormone-binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins in the liver, and inhibits the secretion of follicle-stimulating hormone (FSH) from the anterior pituitary. The combined use of estrogen and progesterone can suppress the hypothalamic-pituitary system, reducing the secretion of gonadotropin-releasing hormone (GnRH). Estrogens used in treatment…are readily absorbed through the skin, mucous membranes, and gastrointestinal tract. When used for local action, absorption is usually sufficient to cause systemic effects. /Estrogen/ Gynecomastia has been observed in factory workers who handled Dienestrol without wearing gloves. /Dixemestrol/ The urinary excretion rate of estrogen is very similar regardless of whether the drug is administered orally or intravenously, indicating that most estrogens are rapidly and fairly completely absorbed from the gastrointestinal tract. /Estrogens/
Estrogens are almost insoluble in water. When dissolved in oil and injected, they are rapidly absorbed and metabolized. …Estrogen inactivation mainly occurs in the liver. /Estrogens/
For more complete data on the absorption, distribution, and excretion of Dienestrol (10 types), please visit the HSDB record page.

---

Metabolism/Metabolites
Liver.
Dendrolide is converted to Dienestrol-β-D-glucuronide in rabbits.
Dendrolide is a known metabolite of Dienestrol in primates and mice; it is converted to ω-hydroxy-Dienestrol and excreted in conjugated form…Dienestrol glucuronide is excreted in the urine of rabbits orally administered Dienestrol…
Dienestrol glucuronide is excreted in the urine of rabbits orally administered Dienestrol…

Protein Binding
50% to 80%

---

Interactions Concomitant use with estrogen may alter the metabolism and protein binding of glucocorticoids, leading to decreased clearance, prolonged elimination half-life, and enhanced therapeutic and toxic effects. Estrogen may cause amenorrhea and interfere with the efficacy of bromocriptine. /Estrogen/ Calcium supplements: Concomitant use with estrogen may increase calcium absorption. /Estrogen/ Concomitant use with estrogen may enhance the anti-inflammatory effects of adrenocorticotropic hormone-induced endogenous cortisol. /Estrogen/ For more complete data on DIENESTROL (9 interactions in total), please visit the HSDB record page.

[1]. J Chromatogr B Analyt Technol Biomed Life Sci . 2014 Apr 15:957:7-13.

Dienestrol (DES) is an olefin compound with the structure hex-2,4-diene, substituted with 4-hydroxyphenyl groups at the 3 and 4 positions, respectively. It is an exogenous estrogen, belonging to the phenolic and olefinic compounds. DES is a synthetic nonsteroidal estrogen and an estrogen receptor agonist. Part of the mechanism of action of estrogen is to increase vaginal secretions, keeping the vagina and urethra healthy. Using or applying estrogen can relieve or reduce symptoms such as vaginal dryness and pain, vulvar itching, redness, or pain. Vaginal estrogen can be used to treat conditions including vulvar dermatitis (vulvar atrophy), vaginitis (atrophic vaginitis), and urethritis (atrophic urethritis). It has been reported that magnolia (Magnolia obovata) contains DES, and relevant data exists. DES is a synthetic nonsteroidal estrogen with a structure related to Dienestrol. It is commonly used in cream form to treat menopausal and postmenopausal symptoms. Drug Indications For the treatment of atrophic vaginitis and vulvar atrophy. Mechanism of Action Dienestrol (DES) is a synthetic nonsteroidal estrogen. Estrogen passively diffuses into target cells, binds to estrogen receptors, enters the cell nucleus, and binds to DNA, initiating or enhancing gene transcription for protein synthesis. Estrogen first binds with a very high affinity to the 8S receptor protein in the cytoplasm, which then dissociates into a 4S receptor carrying estrogen. ... The estrogen complex is converted to a 5S receptor and transported to the cell nucleus, ultimately binding to DNA. Synthetic Estrogen The activity of synthetic estrogen depends on the presence of its terminal hydroxyl group. The hydroxyl group participates in binding to specific receptor proteins present in the cytosol of target organ cells. At the cellular level, estrogen can increase the synthesis of DNA, RNA, and various proteins in responding tissues. Estrogen can reduce the release of hypothalamic gonadotropin-releasing hormone (GnRH), thereby leading to a decrease in the release of pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH). /Estrogen/

---

Therapeutic Uses
Nonsteroidal Estrogens
Dienestrol, like Stilbestrol, is a nonsteroidal estrogen derived from stilbene. It can be taken orally or applied topically. Oral dienestrol offers no advantage over other oral estrogens, and there are currently no oral formulations available. Dienestrol is primarily used as an intravaginal cream to treat atrophic vaginitis or prepubertal vulvovaginitis.
Pharmaceuticals (Veterinary): Synthetic estrogen. Diacetate form was used in feeding trials. Parenteral administration is used to treat functional infertility, i.e., insufficient estrogen required for follicle stimulation and maturation in bovine (and occasionally equine) ovaries. Oral administration is used in chickens and turkeys to improve meat quality and appearance through proper fat distribution.
Pharmaceuticals (Veterinary): Increases fatty liver and serum calcium content in chickens while reducing bone fragility. Can be used intravaginally and intrauterinely to help restore normal epithelial growth.
For more complete data on the therapeutic uses of Dienestrol (10 in total), please visit the HSDB record page.

---

Drug Warnings
Drug estrol is contraindicated during pregnancy.
...A disadvantage of some synthetic estrogen compounds is that nausea may occur after use...at the lowest effective dose for some women, but...more than 20% of women using such products with caution experience this. For these women, natural products must be used instead of synthetic materials. /Synthetic Estrogens/
Drug estrol has not been shown to have any therapeutic effect during pregnancy, and its use by pregnant women may cause serious harm to the fetus.
Drug estrol is toxic like other estrogens, and the usual precautions, precautions, and contraindications associated with estrogen therapy should be followed.
For more complete data on the drug warnings of Dienestrol (18 in total), please visit the HSDB record page.

---

Pharmacodynamics
Estrogens diffuse to target cells and interact with protein receptors. Target cells include the female reproductive tract, mammary glands, hypothalamus, and pituitary gland. Estrogen can increase the liver's synthesis of sex hormone-binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins, and inhibit the anterior pituitary gland's secretion of follicle-stimulating hormone (FSH). The combined use of estrogen and progesterone can suppress the hypothalamic-pituitary system, reducing the secretion of gonadotropin-releasing hormone (GnRH).

C18H18O2

266.3343

266.131

C, 81.17; H, 6.81; O, 12.01

84-17-3

Dienestrol-d2;1346606-45-8

667476

White to off-white crystalline powder

1.129 g/cm3

395.4ºC at 760 mmHg

229ºC

181.4ºC

1.4800 (estimate)

4.604

2

2

3

20

318

0

OC1C=CC(C(C(C2C=CC(O)=CC=2)=CC)=CC)=CC=1

NFDFQCUYFHCNBW-SCGPFSFSSA-N

InChI=1S/C18H18O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h3-12,19-20H,1-2H3/b17-3+,18-4+

4-[(2E,4E)-4-(4-hydroxyphenyl)hexa-2,4-dien-3-yl]phenol

Dehydrostilbestrol; Restrol; Sexadien; Dienoestrol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~155 mg/mL (~582 mM)

Solubility in Formulation 1: 2.08 mg/mL (7.81 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (7.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (7.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)